The long-term goal of the proposed research is to define the mechanisms of hyperlipoproteinemia in diabetes mellitus by studying both diabetic patients and animal models of diabetes. In patients with fasting hyperglycemia without ketoacidosis, we will study very low density lipoprotein (VLDL) triglyceride (TG) kinetics by two methods (H3-glycerol and protamine sulfate). Estimates of VLDL-TG removal will be made by measuring tissue lipoprotein lipase (LPL). Rats with diabetes mellitus will be produced by streptozotocin and animals with both mild and severe hyperglycemia will be studied. Overall VLDL-TG production rate will be estimated with Triton WR 1339, and the role of the liver and intestine in VLDL-TG production separately estimated by combined ultrastructural, physiological and biochemical studies. Overall VLDL-TG removal rate will be estimated by the rate of disappearance of prelabeled VLDL-TG from the plasma of control and diabetic rats. Specific defects of lipoprotein removal in diabetes will be investigated by using muscle perfusion to study the rate at which partially delipidated particles ("remnants") are produced, liver perfusion to determine the rate at which remnants are metabolized, and measurement of tissue LPL to relate these kinetic findings to changes in enzyme activity.